Biological sample processing

ABSTRACT

Systems and methods are provided for processing a biological sample. In one embodiment, the method comprises receiving a sample vessel containing the sample; retrieving information from an information storage unit associated with the sample; using said information for selecting at least one cartridge front at least two or more different cartridges, each configured for use with a sample processing device; loading at least one or more reagents onto the cartridge, wherein the one or more reagents to be added are selected based at least in part on the information or instructions derived from the information; and placing the sample vessel in the cartridge.

BACKGROUND

Analysis of biological samples from a subject may be important forhealth-related diagnosing, monitoring and/or treating of the subject. Avariety of methods are known for the analysis of biological samples.However, in order to provide better diagnosing, monitoring, and/ortreating of subjects, improvements in the analysis of biological samplesare desired. Current techniques have various limitations, including butnot limited to wasted reagents/materials, lack of flexibility in testmenu, and/or low throughput/high cost associated with sample analysis.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.However, in the event of a conflict between the content of the presentexpress disclosure and the content of a document incorporated byreference herein, the content of the present express disclosurecontrols.

SUMMARY

The disadvantages associated with the prior art are overcome by at leastsome embodiments described herein.

In one embodiment, a method is provided for processing a biologicalsample, the method comprising: receiving a sample vessel containing thesample; retrieving information from an information storage unitassociated with the sample; using said information for selecting atleast one cartridge from at least two or more different cartridges, eachconfigured for use with a sample processing device; loading at least oneor more reagents onto the cartridge, wherein the one or more reagents tobe added are selected based at least in part on the information orinstructions derived from the information; and placing the sample vesselin the cartridge.

It should be understood that one or more of the following features maybe adapted for use with any of the embodiments described herein. Forexample and not limitation, retrieving the information may compriseusing optical scanning to obtain information from the informationstorage unit. Optionally, retrieving comprises using electromagnetictechniques to obtain information front the information storage unit.Optionally, the information storage unit is on the sample vessel.Optionally, the information storage unit is on the sample vessel and/ora test order. Optionally, the information storage unit comprises a barcode. Optionally, the information storage unit comprises a QR code.Optionally, the information storage unit comprises aradiofrequency-based storage unit. Optionally, the method comprisescommunicating the information from to an external device. Optionally,the method comprising receiving from the external device instructionsfor cartridge assembly. Optionally, the receiver may be a communicationsunit at or near the cartridge assembly location. Optionally, theinformation comprises cartridge assembly instructions. Optionally, theinformation comprises information regarding components that are to beincluded in the cartridge. Optionally, the information comprisesinformation specifying which cartridge to select. Optionally, theinformation comprises information specifying which tests are to beperformed on the sample. Optionally, at least one of the cartridges ispartially loaded with some components prior to being selected.Optionally, at least one of the cartridges comprises a frame withoutother cartridge components prior to being selected for cartridgeassembly. Optionally, at least one of the cartridges comprises a framewithout other cartridge components therein prior to the cartridge beingselected for cartridge assembly.

Optionally, the cartridge comprises at least one absorbent pad.Optionally, the two or more different cartridges each has a differentconfiguration for holding the reagents. Optionally, the two or moredifferent cartridges each defines one or more locations for receivingone or more reagent vessels. Optionally, the two or more differentcartridges each defines one or more locations for receiving one or morediluent vessels. Optionally, the two or more different cartridges eachdefines one or more locations for receiving one or more pipette tips.Optionally, the two or more different cartridges each defines one ormore locations for receiving one or more reaction vessels. Optionally,the two or more different cartridges each defines one or more locationsfor receiving one or more cuvettes. Optionally, the two or moredifferent cartridges each defines one or more locations for receivingone or more arrays of reagents. Optionally, the two or more differentcartridges each defines one or more locations for receiving one or morearrays of diluents. Optionally, the two or more different cartridgeseach defines one or more locations for receiving one or more arrays ofpipette tips. Optionally, the two or more different cartridges eachdefines one or more locations for receiving one or more arrays ofreaction vessels. Optionally, the two or more different cartridges eachdefines one or more locations for receiving one or more arrays ofcuvettes. Optionally, the method comprises using one or morepick-and-place robots to add the reagents to the cartridge. Optionally,at least one robot is a delta robot. Optionally, at least one robot is aD3 delta robot. Optionally, at least one robot is a D4 delta robot.Optionally, at least one robot is a D5 delta robot. Optionally, at leastone robot is a D6 delta robot. Optionally, the robot is position in anoverhead position over the cartridge assembly area.

Optionally, the cartridge has a structure that can be used to registerthe cartridge with the sample processing device for desired positioningof the cartridge. Optionally, this may be one or more protrusions on thecartridge. Optionally, this may be one or more indentations on thecartridge. Optionally, some embodiments may use a combination of theforegoing for registration purposes. Optionally, each of the two or moredifferent cartridges has the structure to register the cartridge withthe sample processing device. Optionally, the structure comprises anangled structure for alignment of the cartridge with a tray in thesample processing device. Optionally, a visual mark on the cartridge isused for positioning the cartridge in a cartridge receiving location ofthe sample processing device.

Optionally, the method comprises transporting the cartridge with thesample vessel and one or more reagents therein or thereon, from acartridge assembly location to a sample processing location. Optionally,the method comprises transporting two or more cartridge simultaneouslyfrom a cartridge assembly location to a sample processing location.Optionally, the method comprises operably coupling the assembly locationwith the sample processing location with a transport assembly.Optionally, the transport assembly comprises a self-propelled robotconfigured to transport one or more cartridges from the assemblylocation to the sample processing location. Optionally, at least one endeffector is on the robot for handling the cartridge. Optionally, atleast one end effector for loading components into the cartridge.Optionally, the transport assembly comprises a conveyor-belt basedsystem for transporting the cartridge. Optionally, the method comprisesusing a cartridge loading assembly to move a cartridge from thetransport assembly to at least one sample processing device. Optionally,the method comprises using a cartridge loading assembly to move acartridge from the transport assembly to cartridge receiving locationfor at least one sample processing device. Optionally, the methodcomprises using a cartridge loading assembly to move a cartridge fromthe transport assembly to one of a plurality of cartridge receivinglocations that leads to one or more sample processing devices.Optionally, a plurality of sample processing devices are located at theprocessing location. Optionally, the sample processing devices arearranged in an array configuration. Optionally, the sample processingdevices are arranged in a semi-circular array configuration about acartridge loading assembly.

In one non-limiting example, a method is provided for processing abiological sample, the method comprising: retrieving information from aninformation storage unit associated with a cartridge configured for usewith a sample processing device; loading the cartridge comprising one ormore reagents and the sample vessel into the sample processing device,wherein the loading comprises using a robotic manipulator mounted on atransport having a thermally controlled storage area housing a pluralityof the cartridges, each cartridge having a sample from a differentsubject. Optionally, some embodiments may have cartridges that eachcontain at least two samples from the same subject, wherein each samplecontains a different preparatory agent such as but not limited todifferent anti-coagulants.

Other goals and advantages of the methods, devices, and systemsdescribed will be further appreciated and understood when considered inconjunction with the following description and accompanying drawings.While the following description may contain specific details describingparticular embodiments, this should not be construed as limitations tothe scope of the invention but rather as an exemplification ofpreferable embodiments. For each aspect of the invention, manyvariations are possible as suggested herein that are known to those ofordinary skill in the art. A variety of changes and modifications can bemade within the scope of the invention without departing from the spiritthereof.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings,

FIG. 1 shows an embodiment of a system provided herein.

FIG. 2 shows an embodiment of a system provided herein.

FIG. 3 shows an embodiment of a system provided herein.

FIG. 4 shows an embodiment of a system provided herein.

FIG. 5 shows an embodiment of a system provided herein.

It is noted that the drawings and elements therein are not necessarilydrawn to shape or scale. For example, the shape or scale of elements ofthe drawings may be simplified or modified for ease or clarity ofpresentation. It should further be understood that the drawings andelements therein are for exemplary illustrative purposes only, and notbe construed as limiting in any way.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the invention, as claimed. It may be notedthat, as used in the specification and the appended claims, the singularforms “a”, “an” and “the” include plural referents unless the contextclearly dictates otherwise. Thus, for example, reference to “a material”may include mixtures of materials, reference to “a compound” may includemultiple compounds, and the like. References cited herein are herebyincorporated by reference in their entirety, except to the extent thatthey conflict with teachings explicitly set forth in this specification.

In this specification and in the claims which follow, reference will bemade to a number of terms which shall be defined to have the followingmeanings:

“Optional” or “optionally” means that the subsequently describedcircumstance may or may not occur, so that the description includesinstances where the circumstance occurs and instances where it does not.For example, if a device optionally contains a feature for a samplecollection unit, this means that the sample collection unit may or maynot be present, and, thus, the description includes both structureswherein a device possesses the sample collection unit and structureswherein sample collection unit is not present.

As used herein, the terms “substantial” means more than a minimal orinsignificant amount; and “substantially” means more than a minimally orinsignificantly. Thus, for example, the phrase “substantiallydifferent”, as used herein, denotes a sufficiently high degree ofdifference between two numeric values such that one of skill in the artwould consider the difference between the two values to be ofstatistical significance within the context of the characteristicmeasured by the values. Thus, the difference between two values that aresubstantially different from each other is typically greater than about10%, and may be greater than about 20%, preferably greater than about30%, preferably greater than about 40%, preferably greater than about50% as a function of the reference value or comparator value.

As used herein, a “sample” may be but is not limited to a blood sample,or a portion of a blood sample, may be of any suitable size or volume,and is preferably of small size or volume. In some embodiments of theassays and methods disclosed herein, measurements may be made using asmall volume blood sample, or no more than a small volume portion of ablood sample, where a small volume comprises no more than about 5 mL; orcomprises no more than about 3 mL; or comprises no more than about 2 mL;or comprises no more than about 1 mL; or comprises no more than about500 μL; or comprises no more than about 250 μL; or comprises no morethan about 100 μL; or comprises no more than about 75 μL; or comprisesno more than about 50 μL; or comprises no more than about 35 μL; orcomprises no more than about 25 μL; or comprises no more than about 20μL; or comprises no more than about 15 μL; or comprises no more thanabout 10 μL or comprises no more than about 8 μL; or comprises no morethan about 6 μL; or comprises no more than about 5 μL; or comprises nomore than about 4 μL; or comprises no more than about 3 μL; or comprisesno more than about 2 μL; or comprises no more than about 1 μL; orcomprises no more than about 0.8 μL, or comprises no more than about 0.5μL; or comprises no more than about 0.3 μL; or comprises no more thanabout 0.2 μL; or comprises no more than about 0.1 μL; or comprises nomore than about 0.05 μL; or comprises no more than about 0.01 μL.

As used herein, the term “point of service location” may includelocations where a subject may receive a service (e.g. testing,monitoring, treatment, diagnosis, guidance, sample collection, IDverification, medical services, non-medical services, etc.), and mayinclude, without limitation, a subject's home, a subject's business, thelocation of a healthcare provider (e.g., doctor), hospitals, emergencyrooms, operating rooms, clinics, health care professionals' offices,laboratories, retailers [e.g. pharmacies (e.g., retail pharmacy,clinical pharmacy, hospital pharmacy), drugstores, supermarkets,grocers, etc.], transportation vehicles (e.g. car, boat, truck, bus,airplane, motorcycle, ambulance, mobile unit, fire engine/truck,emergency vehicle, law enforcement vehicle, police car, or other vehicleconfigured to transport a subject from one point to another, etc.),traveling medical care units, mobile units, schools, day-care centers,security screening locations, combat locations, health assisted livingresidences, government offices, office buildings, tents, bodily fluidsample acquisition sites (e.g. blood collection centers), sites at ornear an entrance to a location that a subject may wish to access, siteson or near a device that a subject may wish to access (e.g., thelocation of a computer if the subject wishes to access the computer), alocation where a sample processing device receives a sample, or anyother point of service location described elsewhere herein.

In some embodiments, provided herein are systems and methods forprocessing a biological sample.

In some embodiments, with reference to FIG. 1, a vessel 101 containing asample such as but not limited to a biological sample may be positionedin or near an automated robotic system 111 configured for preparingcartridges for use with a sample processing device. In this non-limitingexample, the vessel include an information storage unit such as butlimited to labeling the cartridge with an identifier 102. The automatedrobotic system Ill may contain a local controller 112 and acommunication assembly 113. The automated robotic system 111 may containor be in communication with an identifier detector 114. The automatedrobotic system 111 may be in communication with an external device 115via the communication assembly 113. The identifier detector 114 maydetect the identifier 102 on the vessel 101. Based on information in theidentifier 102, the local controller 112 may execute a protocol for theautomated robotic system 111 to prepare a cartridge containing thevessel 101. The automated robotic system 111 may load the vessel 101into a cartridge. The cartridge may be selected from a plurality ofcartridges 121, 131. The automated robotic system 111 may further loadone or more reagent-containing or empty vessels 122, 123, 124, 132, 133into the cartridge containing the biological-sample containing vessel101. A cartridge 121, 131 may be configured to receive certain reagentsor vessels having certain shapes. For example, cartridge 121 may beconfigured to only receive vessels 122, 123, and 124, whereas cartridge132 may be configured to only receive vessels 132 and 133. Prior to theloading of the biological sample-containing vessel 101 into thecartridge, the cartridges 121, 131 and reagent-containing and emptyvessels 122, 123, 124, 132, 133 may be stored in the automated roboticsystem 111, or they may be stored near the automated robotic system 111such that they are accessible to the system 111. A cartridge 121, 131may have at least one information storage unit such as but not limitedto an identifier 125, 135 on the cartridges, respectively. Although thisnon-limiting example is shown loading the sample containing vessel 101into the cartridge, it should be understood that some embodiments mayload the sample containing vessel 101 into the cartridge at a laterpoint in time, or in some alternative embodiments, not at all. Althoughthis non-limiting example is shown loading one sample containing vessel101 into the cartridge, other embodiments may load two or more samplecontaining vessels 101 into the cartridge. Optionally, some embodimentsmay have a single structure that may contain a plurality of samplecontaining vessels 101.

In a system or method described herein, a biological sample may beprovided. The sample may include one or more fluid components. In someinstances, solid or semi-solid samples may be provided. Optionally, thesample may be from a subject. A subject may be a human or an animal. Thesample may include a bodily fluid, secretion, or tissue of a subject.The biological sample may be a bodily fluid, a secretion, or a tissuesample. Examples of biological samples may include but are not limitedto, blood, serum, saliva, urine, gastric and digestive fluid, tears,stool, semen, vaginal fluid, interstitial fluids derived from tumoroustissue, ocular fluids, sweat, mucus, earwax, oil, glandular secretions,breath, spinal fluid, hair, fingernails, skin cells, plasma, nasal swabor nasopharyngeal wash, spinal fluid, cerebral spinal fluid, tissue,throat swab, biopsy, placental fluid, amniotic fluid, cord blood,emphatic fluids, cavity fluids, sputum, pus, microbiota, meconium,breast milk or other excretions. Samples may be front a plant,microorganism e.g. virus, bacteria), or other biological material.

In some embodiments, a biological sample may be in a vessel or othercontainer. In some embodiments, a biological sample is in a vessel whichhas an interior volume of no greater than 200 ml, 100 ml, 50 ml, 40 ml,30 ml, 20 ml, 10 ml, 5 ml, 4 ml, 3 ml, 2 ml, 1 ml, 900 μl, 700 μl, 600μl, 500 μl, 400 μl, 300 μl, 200 μl, 100 μl, 75 μl, 50 μl, 40 μl, 30 μl,20 μl, 10 μl, 5 μl, 4 μl, 3 μl, 2 μl, or 1 μl. In some embodiments, abiological sample is in a vessel having any of the features of asample-containing vessel described in any of the documents incorporatedby reference elsewhere herein.

In some embodiments, a vessel containing a biological sample may belabeled with information storage unit such as but not limited to anidentifier. In one non-limiting example, the vessel may be but is notlimited to vessel 101. The identifier may be any structure or system forconveying information, such as but not limited to a bar code, aformation of lines or shapes, a series of alphanumerical characters, aradio frequency tag, or a physical structure (e.g. raised bumps ordepressions in a surface). In some embodiments, the identifier maycontain a storage or memory device and can transmit information to anidentifier detector. An identifier may contain or be linked toinformation relating to, for example, any one or more of the identity ofthe subject from whom the biological sample was obtained, the time,date, or location of collection of the sample from a subject, thehealthcare provider who requested the assays to be performed on thebiological sample, which assays are to be performed on the biologicalsample, the type of cartridge to use with the biological sample, vesselsto load into the cartridge with the biological sample, or reagents toload into the cartridge with the biological sample. In some embodiments,any of the above information is provided in the identifier itself. Insome embodiments, an identifier may contain a code or other informationwhich may be processed by an appropriate program to reveal any of theabove information. In some embodiments, more than one identifier or typeof identifier may be included in a vessel. An identifier may be added toa vessel prior to a biological sample being added to the vessel.Alternatively, an identifier may be added to a vessel after thebiological sample is added to the vessel.

In one non-limiting example, a biological sample may be positioned in ornear an automated robotic system configured for preparing cartridges foruse with a sample processing device. In some embodiments, a biologicalsample is collected at a remote location, and transported to theautomated robotic system. In other embodiments, a biological iscollected near the automated robotic system. In some embodiments, abiological sample may be collected or transported to an automatedrobotic system according to system or method as described in any of thedocuments incorporated by reference elsewhere herein.

In a system or method described herein, an automated robotic systemconfigured for preparing cartridges for use with a sample processingdevice may be provided. In some embodiments, the automated roboticsystem may contain a local controller. The local controller may beconfigured to control the movement of one or more parts of the automatedrobotic system. The local controller may contain a local memory. Thelocal memory may contain tangible computer readable media with code,instructions, language to perform one or more steps as describedelsewhere herein. The local memory may store one or more protocols. Theprotocols may be generated locally on the automated robotic system, ormay be received from an external source (e.g. a cloud-based database, aUSB drive, etc.)

In some embodiments, an automated robotic system may contain acommunication assembly. The communication assembly may be part of or maybe in communication with the local controller. The communicationassembly may be configured to communicate with an external device. Insome embodiments, the communication assembly may be configured towirelessly communicate with an external device (e.g. with Bluetooth orRTM technology). In some embodiments, the communication assembly maycommunicate with an external device via a cellular or satellite network.

In some embodiments, an automated robotic system may be in communicationwith an external device. In some embodiments, the external device can bea computer system, server, or other electronic device capable of storinginformation or processing information. In some embodiments the externaldevice includes one or more computer systems, servers, or otherelectronic devices capable of storing information or processinginformation. In some embodiments, the external device can include moreservers as are known in the art and commercially available. Such serverscan provide load balancing, task management, and backup capacity in theevent of failure of one or more of the servers or other components ofthe external device, to improve the availability of the server. A servercan also be implemented on a distributed network of storage andprocessor units, as known in the art, wherein the data processingaccording to the present invention reside on workstations such ascomputers, thereby eliminating the need for a server. In someembodiments, an external device may be a cloud-computing based system.

In some embodiments, an automated robotic system may contain or be incommunication with an identifier detector. An identifier detector maydetect an identifier on a vessel containing a biological sample. Forexample, an identifier detector may be a bar-code scanner or art RFIDreader. In some embodiments, an identifier detector may contain an LEDthat emits light which can interact with an identifier which reflectslight and which can be measured by the identifier detector to determineinformation provided in the identifier. In some embodiments, theidentifier detector may be in communication with the local controller ofthe automated robotic system, such that information relating to anidentifier on a vessel is transmitted from the identifier detector tothe local controller.

In some embodiments, the automated robotic system may be or may containa pick-and-place robot. In one non-limiting example, the pick-and-placerobot may be a delta robot. The pick-and-place robot may be or have oneor more characteristics of a pick-and-place robot available from, forexample, ABB, Inc. (Zurich, Switzerland), Bastian Solutions(Indianapolis, Ind.), Codian Robotics (Veenendaal, Netherlands), Yaskawa(Eschborn, Germany), or Oystar (Lorenzstrasse, Germany). Of course, itshould be understood that other automation systems, methods, or devices,including those that may be developed in the future, are not excludedfor use with system(s), methods, or devices described herein.

In some embodiments, an automated robotic system may contain or havephysical access to one, two, three or more cartridges. The cartridgesmay be configured to support one or more different vessels, includingbiological sample-containing vessel, reagent-containing vessels, andempty vessels. Vessels may include, for example, tips, containers,cuvettes, assay units, reagent units, processing units etc. In someembodiments, an automated robotic system may contain or have physicalaccess to one, two, three, four, five or more different types ofcartridges having different configurations for supporting vessels. Forexample, one type of cartridge may have a configuration such that it cansupport 100 vessels which each hold a volume of 50 microliters, whereasanother type of cartridge may have a configuration such that it cansupport 10 vessels which each hold a volume of 100 microliters and 20vessels which each hold a volume of 200 microliters. In another example,one type of cartridge may have a configuration such that it can supportthree microscopy cuvettes and 10 pipette tips, whereas another type ofcartridge may have a configuration such that it can support 8 nucleicacid amplification vessels and 20 pipette tips. In another example, onetype of cartridge may have a configuration such that it can supporthexagonal-shaped vessels, whereas another type of cartridge may have aconfiguration such that it can support round-shaped vessels. Of course,other numbers, not specifically enumerated above, may also be configuredfor use with the systems, devices, and methods described herein.

In some embodiments an automated robotic system may contain or havephysical access to one, two, three or more empty or reagent-containingvessels. In some embodiments, the empty or reagent-containing vesselsmay have any of the characteristics of empty or reagent-containingvessels as described in any of the documents incorporated by referenceelsewhere herein. In some embodiments, the reagent-containing vesselsmay contain antibodies, nucleic acids, enzymes, dyes, buffers, salts,chromogens, or other reagents for performing assays related tobiological samples. In some embodiments, vessels may contain a mixtureof more than one reagent. In some embodiments, an automated roboticsystem may contain or have physical access to 1, 2, 3, 4, 5, 10, 20, 30,40, 50, 100, 150, 200, 300, 400, 500, 1000, or more reagents, alone orin combination. In some embodiments, the reagent-containing vessels maycontain any of the reagents described in any of the documentsincorporated by reference elsewhere herein.

In some embodiments, prior to being loaded into the automated roboticsystem or placed in the vicinity thereof, the cartridges do not containany empty or reagent-containing vessels. In other embodiments, thecartridges are fully loaded with empty and reagent-containing vesselssufficient to perform one or more assays with a biological sample priorto being loaded into the automated robotic system or placed in thevicinity thereof. In other embodiments, the cartridges partially loadedwith some empty or reagent-containing vessels prior to being loaded intothe automated robotic system or placed in the vicinity thereof. In someembodiments, the cartridges are loaded with empty vessels prior to beingloaded into the automated robotic system or placed in the vicinitythereof.

Optionally, the automated robotic system may contain a housing, and oneor more components of the system described herein may be inside thehousing.

In some embodiments, a vessel containing a biological sample is loadedinto an automated robotic system configured for preparing cartridges foruse with a sample processing device. In some situations, a vesselcontaining a biological sample may be manually loaded by a human intothe automated robotic system. In other embodiments, an automated roboticsystem may be configured to transport a vessel containing a biologicalsample from outside the system into the automated robotic system. Forexample, an automated robotic system may contain a pick-and-place robotwhich is configured to pick up a biological sample which is positionedoutside of the system, and to move it into the system.

In some embodiments, a single vessel containing a biological sample isloaded into an automated robotic system at a time. In other embodiments,multiple vessels containing biological samples may be loadedsimultaneously into an automated robotic system. For example, a rack orother structure which supports multiple vessels (e.g. 2, 3, 4, 5, 10,15, 20, 30, 40, 50, 100, or more) may be loaded into an automatedrobotic system, thereby simultaneously transporting multiple vesselsinto the system at a time.

Optionally, an identifier on a vessel containing a biological sample maybe detected by an identifier detector when a vessel is outside or insidean automated robotic system.

In some embodiments, an automated robotic system may prepare a cartridgecontaining a vessel containing a biological sample, based on informationpresent in the identifier on the vessel and obtained by the identifierdetector. For example, an identifier detector may detect information inan identifier on a vessel, this information may be communicated to thelocal controller of an automated robotic system, and based on thisinformation, and the local controller may execute a protocol stored in alocal memory on the automated robotic system for preparing a cartridgecontaining the vessel. In another example, an identifier detector maydetect information in an identifier on a vessel, this information may becommunicated to the local controller of an automated robotic system,this information may be further communicated to an external device viathe communication assembly of the automated robotic system, based onthis information, the external device may transmit a protocol to localcontroller via the communication assembly, and the local controller maythen execute the protocol from the external device for preparing acartridge containing the vessel.

In some embodiments, based on a protocol to prepare a cartridgecontaining a biological sample-containing vessel, the automated roboticsystem may load the sample-containing vessel into a cartridge of acertain type, wherein the cartridge is selected from one, two, three,four, five or more different types of cartridges having differentconfigurations for supporting vessels which are contained in or arephysically accessible to the automated robotic system. A protocol maydirect that a sample-containing vessel be loaded into a certaincartridge type for one or more reasons, such as: the types of assaysthat are to be performed with the biological sample, the types or shapesof vessels that are to be used with assays with the biological sample,the type of sample processing device that is to receive the cartridgecontaining the biological sample, or which specific sample processingdevice is to receive the cartridge containing the biological sample.

In some embodiments, based on a protocol to prepare a cartridgecontaining a biological sample-containing vessel, the automated roboticsystem may load the sample-containing vessel into a certain specificcartridge, wherein the cartridge is selected from 1, 2, 3, 5, 10, 20,50, or more different specific cartridges which are contained in or arephysically accessible to automated robotic system. A protocol may directthat a sample-containing vessel be loaded into a certain specificcartridge for one or more reasons, such as: the specific cartridge maycontain an identifier with information related to the biological sample,the specific cartridge may be pre-loaded with one or more empty orreagent-containing vessels for performing one or more specific assays ora specific group of assays with the sample, or any of the reasonsprovided above for loading a biological sample-containing vessel into acertain type of cartridge.

In some embodiments, based on a protocol to prepare a cartridgecontaining a biological sample-containing vessel, the biologicalsample-containing vessel is loaded into a cartridge before empty orreagent-containing vessels are loaded into the cartridge. In otherembodiments, the biological sample-containing vessel is loaded into acartridge after all empty or reagent-containing vessels for performingone or more assays of interest are loaded into the cartridge. In stillother embodiments, the biological sample-containing vessel is loadedinto a cartridge after some empty or reagent-containing vessels areloaded into the cartridge, but prior to the loading of all empty orreagent-containing vessels for one or more assays of interest into thecartridge. In some embodiments, cartridges are provided to an automatedrobotic system containing some or all of the empty or reagent-containingvessels for performing one or more selected assays with a biologicalsample pre-loaded in the cartridge. In other embodiments, cartridges areprovided to an automated robotic system without any of the empty orreagent-containing vessels for performing one or more selected assayswith a biological sample pre-loaded in the cartridge.

In some embodiments, based on a protocol to prepare a cartridgecontaining a biological sample-containing vessel, the automated roboticsystem may load one or more empty or reagent-containing vessels into aselected cartridge. The empty or reagent-containing vessels may beloaded by the automated robotic system into a selected cartridge priorto, during, or after the loading of the biological sample-containingvessel into the cartridge. 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 100, 150,200, 300, 400, 500, or more different empty or reagent-containingvessels may be loaded into a selected cartridge by the automated roboticsystem. 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 100, 150, 200, 300, 400, 500or more different empty or reagent-containing vessels may be loaded intoa selected cartridge by the automated robotic system, wherein the emptyor reagent-containing vessels are selected from 1, 2, 3, 4, 5, 10, 20,30, 40, 50, 100, 150, 200, 300, 400, 500, 1000, 2000, 5000, or moredifferent empty or reagent-containing vessels which are contained in orare physically accessible to automated robotic system. A protocol maydirect that a one or more specific different empty or reagent-containingvessels be loaded into a certain specific cartridge for one or morereasons, such as: the assays to be performed with the biological samplein the cartridge or the specific cartridge or type of cartridge that isto receive the vessels.

In some embodiments, before, during, or after the preparation of acartridge containing a biological sample-containing vessel, theautomated robotic system may add an identifier to the cartridge. Thecartridge identifier may have any of the characteristics or contain anyof the information described elsewhere herein for the identifier on thebiological sample containing vessel. In addition or alternatively, thecartridge identifier may contain information regarding, for example, thetime, date, or location of the addition of the biological sample to thecartridge, the assays to be performed with the cartridge, which type ofsample processing device is to receive the cartridge, or which specificsample processing device is to receive the cartridge.

In some embodiments, a system or method provided herein may include aplurality of sample processing devices. In some embodiments, a sampleprocessing device may be or may contain any of the features of sampleprocessing devices as described in any of the documents incorporated byreference elsewhere herein. In some embodiments, the plurality of sampleprocessing devices may contain at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,20, 30, 40, 50, 100 or more sample processing devices. The plurality ofsample processing devices may be located close to each other. In someembodiments, all of the sample processing devices of the plurality ofdevices are within the same room or building. In some embodiments, allof the sample processing devices of the plurality of devices are withina contiguous area of 1, 2, 3, 4, 5, 10, 15, 20, 30, 50, 100, or 200square meters or less.

In some embodiments, in a system or method provided herein including aplurality of sample processing devices, the system or method may includea transport assembly for transporting sample-containing cartridges to,from, into, or out of one or more sample processing devices. In someembodiments, a transport assembly may be or include a conveyor belt orsimilar structure. In some embodiments, a transport assembly may be orinclude a robot. In some embodiments, the robot may operate on a trackor with the aid guide rail or similar structure. In some embodiments,the robot may operate without a track or guide rail. In someembodiments, the robot may be self-propelled. In some embodiments, acartridge is fully loaded with vessels when the cartridge is loaded ontoa transport assembly. In other embodiments, a cartridge requires one ormore additional empty or reagent-containing vessels to be added to thecartridge before one or more selected assays may be performed with abiological sample with using vessels in the cartridge. In someembodiments, a cartridge is added to a transport assembly prior to avessel containing the biological sample being loaded into the cartridge.

In some embodiments, a transport assembly may contain or be capable ofsupporting a plurality of sample-containing cartridges. By way ofnon-limiting example, a conveyor belt or a robot may contain or becapable of supporting 1, 2, 3, 4, 5, 10, 15, 20, 30, 50, 100 or morecartridges. In one embodiment, these cartridges may be transported inbatch manner. Optionally, some may transport the cartridges in asequential manner.

In some embodiments, with reference to FIG. 2, a system or methodprovided herein may include a plurality of sample processing devices201, 202, 203, 204. One or more devices of the plurality of sampleprocessing devices 201, 202, 203, 204 may be adjacent to another of thesample processing devices 201, 202, 203, 204. One or more devices of theplurality of sample processing devices 201, 202, 203, 204 may have thesame configuration as another of the sample processing devices 201, 202,203, 204. One or more devices of the plurality of sample processingdevices 201, 202, 203, 204 may have a different configuration ascompared with another of the sample processing devices 201, 202, 203,204. A transport assembly 211 may be present in the same room as theplurality of sample processing devices 201, 202, 203, 204. The transportassembly 211 may contain an end-effector 212 for moving a cartridge 213into or out of a sample processing device 201, 202, 203, 204. Thetransport assembly 211 may further contain a storage area 214 forstoring one or more new or used cartridges. It should be understood thatalthough the images of the sample processing devices 201 and 202 areshown to be oriented at an angle to the path followed by the transportassembly 214 in FIG. 2, the devices 201 and 202 may also be oriented tobe orthogonal to the path to facilitate alignment of a cartridge with asample receiving location on the sample processing devices 201 and 202.It should also be understood that the sample receiving locations 222 onthe sample processing devices may be aligned in a straight line, apattern, or other manner as desired to facilitate one or more aspects ofsample handling or processing.

It should also be understood that in some embodiments, the storage area214 may be a thermally controlled storage area, which in onenon-limiting example, may be used to begin acclimating the cartridgestoward a desired temperature range. Optionally, some embodiments may usethe thermally controlled storage area to begin incubation process(es)for one or more of the cartridges. It should be understood that withinthe thermally controlled storage area, there may be at least one regionconfigured for at least one temperature range and at least one otherregion for at least one other temperature range. In one embodiment, eachregion can hold at least one cartridge. Optionally, some may haveregion(s) that hold at least two or more cartridges. Optionally, someembodiments may have each cartridge with its own individuallycontrollable temperature zone. Optionally, some embodiments may beconfigured to control one portion of the cartridge(s) to one temperaturewhile controlling a different portion of the same cartridge(s) to adifferent temperature. In one non-limiting example, a top portion of onearea on the cartridge is exposed to a thermal environment to controlthat area to first temperature while a an underside portion of anotherare of the cartridge is exposed to a second thermal environment tocontrol that area to second temperature different from the firsttemperature. In one embodiment, the storage area 214 may define aplurality of shelves, slots, or other cartridge holding areas which maybe heated in zones or individually to a desired temperature range. Inone embodiment, an information storage unit on or associated with thecartridge may provide temperature and/or other information regarding thecartridge. Some embodiments may use a peltier thermal device, resistivethermal device, phase-change thermal device, or the combinations thereofin the storage area or in each slot of the storage areas.

In one non-limiting example, the storage area 214 may be a removabledevice coupleable to the transport assembly 211 such that a plurality ofcartridge may be loaded or unloaded at one time. In one non-limitingexample, the storage area 214 may be thermally controlled package,backpack, hard-shelled container, soft-shelled container, partiallysoft-shelled container, single or multiple combinations of theforegoing, or other types of containers that may be implemented in thefuture. Some embodiments of the transport assembly 211 may be able tosimultaneously transport two or more units having storage areas 214.Optionally, some embodiments of the transport assembly 211 may have ahopper, flexible conveyor, flexible delivery system, or a chute forreceiving cartridges. Some embodiments may transport one large unit witha storage area 214 and a similar sized or smaller unit with a storm areacontrolled to a different temperature range. Some embodiments may haveunits with nested storage areas 214, perhaps with one controlled to adifferent temperature than the other to assist with acceleratingprocessing. Some embodiments may include a vibration source (constant orperiodic motion) to assist in pre-processing of the sample and/orcartridge while on-board the transport assembly 211. Optionally, someembodiments may include a controlled atmosphere in the storage area 214to assist in preprocessing of the sample and/or to preserve theintegrity of the sample or the cartridge. The control may be by pressureand/or the type of gas in the storage area 214. Optionally, someembodiments may have a separate transport assembly for sample vesselsand another transport assembly for cartridges. Some embodiments may havea transport assembly with one storage area of samples and one forcartridges. Some embodiments may have cartridges being transportedwithout sample vessels and the two are not combined until just beforeinsertion into the sample processing device or they may be insertedseparately into the sample processing device. Optionally, someembodiments of the transport assembly may have at least one storage areathat is cooled below ambient for the sample vessels and at least onestorage area heated to bring the cartridge to a processing temperature.Optionally, both storage areas may be controlled to be heated or cooled.

Optionally, a transport assembly may have a local controller, acommunication assembly, and it may be capable of communicating with anexternal device. In some embodiments, the local controller,communication assembly, and external device may have any of theproperties described elsewhere herein for the local controller,communication assembly, and external device of the automated roboticsystem. In some embodiments, the external device may be same externaldevice with which the automated robotic system communicates.

In some embodiments, with reference to FIG. 3, a cartridge 301 may beintroduced onto a transport assembly which includes a conveyor belt 302.The transport assembly may further contain one or more vessel loadingstations 303, 304. Each vessel loading station 303, 304 may contain apick-and-place robot 305, 306 (e.g. a delta robot) for loading vesselsinto the cartridge 301. The pick-and-place robot may be configured toload empty vessels, reagent-containing vessels, or biologicalsample-containing vessels into a cartridge 301. The cartridge 301 may beloaded with one or more vessels as it travels along the conveyor belt302 so that as it reaches the end of the conveyor belt 302, it is loadedwith all vessels and reagents necessary to perform one or more selectedassays with a biological sample in the cartridge 301 in a sampleprocessing device. In some embodiments, a plurality of sample processingdevices 311, 312, 313, 314, 315, 316, 317 may be present in a system ormethod including a transport assembly which includes a conveyor belt302. At the end of the conveyor belt, a cartridge loading assembly 307may receive the loaded cartridge 301 from the conveyor belt 302. Thecartridge loading assembly 307 may be configured to load a cartridge 301into a sample processing device 311, 312, 313, 314, 315, 316, 317.

In some embodiments, in systems and method provided herein, artautomated robotic system provided herein may be used with a transportassembly provided herein. For example, a vessel containing a biologicalsample may be provided at an automated robotic system and loaded into acartridge as described herein. The cartridge may then be moved to atransport assembly, and from there loaded into a sample processingdevice. In some embodiments, one or more or all of these steps isautomated, such that a biological sample may be analyzed according tosystems and methods provided herein with minimal direct humanintervention.

In some embodiments, a sample-containing vessel, cartridge, sampleprocessing device, blood collection device, sample transport method,empty vessel, reagent-containing vessel, or reagents or may include orhave any of the features of the sample-containing vessel, cartridge,sample processing device, blood collection device, sample transportmethod, empty vessel, reagent-containing vessel, or reagent described inany one or more of U.S. Pat. No. 8,088,593, U.S. patent application Ser.Nos. 13/244,947, 13/769,779, 13/769,817, 13/769,818, 13/769,820, U.S.Provisional Patent Application Nos. 61/766,076, 61/766,113, 61/766,117,61/766,119, 61/697,797, 61/786,351, 61/733,886, all of which are hereinincorporated by reference in their entirety for all purposes. U.S.Patent Application No. 61/805,925 is also fully incorporated herein byreference in its entirety for all purposes.

FIG. 4 shows a still further non-limiting example wherein sampleprocessing devices 311, 312, 313, 314, 315, 316, 317, and 318 may be oneither side of the path 321 to be traveled by the transport assembly211. This shows that the transport assembly 211 may be used to servicesample processing devices on multiple sides of the transport assembly211. Some embodiments may have the transport assembly 211 return to abase station separate from the sample processing devices for loadingand/or unloading of cartridges. There may be a switch path to allow formultiple transport assemblies 211 to be moved onto the path 321. Theswitch may be at a hub such as but not limited to the base stationwherein a turn table, switching track, or other device can allow formultiple transport assemblies 211 to be moved onto the same pathway.Optionally, some embodiments may not have a path but instead use atrackless surface wherein the transport assemblies have other guidancesystems to travel along a designated path. Optionally, some may usevision, IR, and/or other systems to autonomously navigate to the correctlocation. Some embodiments may have transport assemblies operating alongparallel “tracks” 321 and 322 in front of the two banks of sampleprocessing devices.

Referring now to FIG. 5, a still further embodiment is shown of at leasta portion of art end-effector that may be used with the transportassembly 211. FIG. 5 is a top-down view of the end effector 500 whereinit may be included as part of a robotic arm or other manipulator. Thistop-down view of this non-limiting example shows that there may be anillumination source 502 for use with a detector 504 such as but notlimited to a camera (IR, visual, or other). This guidance system can beused to assist with positioning of jaw 506 of the end-effector 500 toengage a cartridge. It can also be used to align the end-effector 500 toallow insertion of the cartridge to a cartridge receiving location. Someembodiments may use an alignment guide to the side or adjacent area 510to the cartridge receiving location that can act as a guide dot,fiducial, or other positioning landmark for alignment of theend-effector. In this non-limiting example, the jaw 506 may be replacedwith a different type of manipulator depending on the shape of thecartridge to be handled. In some embodiments, the jaw 506 may havefeature(s) shaped to be mating with feature(s) on the cartridge.Although the embodiment herein shows a vision system coupled to theend-effector, it should be understood that some embodiments may not havea vision system but instead uses a different guidance technique.Optionally, some embodiments may include a tool such as but not limitedto rod, elongate member, flat spatula-type extension, extendable grips,or the like to assist with insertion and/or removal of a cartridge for atarget location. Some embodiments may have more than one robotic arm ona transport assembly 211. Optionally, some embodiments may have morethan one end-effector on each robotic arm.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. Any feature, whetherpreferred or not, may be combined with any other feature, whetherpreferred or not. It should also be understood that while the inventionprovided herein has been described herein using a limited number ofterms and phrases for purposes of expediency, the invention could alsobe described using other terms and phrases not provided herein whichalso accurately describe the invention. The appended claims are not tobe interpreted as including means-plus-function limitations, unless sucha limitation is explicitly recited in a given claim using the phrase“means for.” It should be understood that as used in the descriptionherein and throughout the claims that follow, the meaning of “a,” “an,”and “the” includes plural reference unless the context clearly dictatesotherwise. For example, a reference to “an assay” may refer to a singleassay or multiple assays. Also, as used in the description herein andthroughout the claims that follow, the meaning of “in” includes “in” and“on” unless the context clearly dictates otherwise. As used in thedescription herein and through the claims that follow, a first objectdescribed as containing “at least a portion” of a second object maycontain the full amount of/the complete second object. As used in thedescription herein and throughout the claims that follow, the terms“comprise”, “include”, and “contain” and related tenses are inclusiveand open-ended, and do not exclude additional, unrecited elements ormethod steps. Finally, as used in the description herein and throughoutthe claims that follow, the meaning of or includes both the conjunctiveand disjunctive unless the context expressly dictates otherwise. Thus,the term “or” includes “and/or” unless the context expressly dictatesotherwise.

This document contains material subject to copyright protection. Thecopyright owner (Applicant herein) has no objection to facsimilereproduction of the patent documents and disclosures, as they appear inthe US Patent and Trademark Office patent file or records, but otherwisereserves all copyright rights whatsoever. The following notice shallapply: Copyright 2013-2014 Theranos, Inc.

What is claimed is:
 1. A method for processing a biological sample, themethod comprising: receiving a sample vessel containing the sample;retrieving information from an information storage unit associated withthe sample; using said information for selecting at least one cartridgefrom at least two or more different cartridges, each configured for usewith a sample processing device; and using an automated robotic systemto load the cartridge and the sample vessel onto a robotic transportassembly for operably coupling a cartridge assembly location with asample processing location of the sample processing device.
 2. Themethod of claim 1 wherein retrieving comprises using optical scanning toobtain information from the information storage unit.
 3. The method ofclaim 1 wherein retrieving comprises using electromagnetic techniques toobtain information from the information storage unit.
 4. The method ofclaim 1 wherein the information storage unit comprises a bar code. 5.The method of claim 1 wherein the information storage unit comprises aQR code.
 6. The method of claim 1 further comprising communicating theinformation from to an external server.
 7. The method of claim 1 whereinthe information comprises information regarding components to beincluded in the cartridge.
 8. The method of claim 1 wherein at least oneof the cartridges is partially loaded with some components prior tobeing selected.
 9. The method of claim 1 wherein the informationcomprises information specifying which tests are to be performed on thesample.
 10. The method of claim 1 wherein the cartridge comprises atleast one absorbent pad.
 11. The method of claim 1 wherein the two ormore different cartridges each defines one or more locations forreceiving one or more reagent vessels.
 12. The method of claim 1 whereinthe two or more different cartridges each defines one or more locationsfor receiving one or more diluent vessels.
 13. The method of claim 1wherein the two or more different cartridges each defines one or morelocations for receiving one or more pipette tips.
 14. The method ofclaim 1 wherein the two or more different cartridges each defines one ormore locations for receiving one or more reaction vessels.
 15. Themethod of claim 1 wherein the two or more different cartridges eachdefines one or more locations for receiving one or more arrays ofreaction vessels.
 16. The method of claim 1 wherein the two or moredifferent cartridges each defines one or more locations for receivingone or more arrays of cuvettes.
 17. The method of claim 1 furthercomprising a plurality of sample processing devices at the sampleprocessing location, wherein the sample processing devices are arrangedin an array configuration.
 18. The method of claim 1 further comprisinga plurality of sample processing devices at the sample processinglocation, wherein the sample processing devices are arranged in asemi-circular array configuration about a cartridge loading assembly.19. A method for processing a biological sample, the method comprising:receiving a sample vessel containing the sample; retrieving informationfrom an information storage unit associated with the sample;communicating the information to an external server; using saidinformation for selecting at least one cartridge from at least two ormore different cartridges, each configured for use with a sampleprocessing device; and using an automated robotic system to load thecartridge and the sample vessel onto a robotic transport assembly foroperably coupling a cartridge assembly location with a sample processinglocation of the sample processing device.
 20. A method for processing abiological sample, the method comprising: receiving a sample vesselcontaining the sample; retrieving information from an informationstorage unit associated with the sample; using said information forselecting at least one cartridge from at least two or more differentcartridges, each configured for use with a sample processing device; andusing an automated robotic system to load the cartridge and the samplevessel onto a robotic transport assembly for operably coupling acartridge assembly location with a sample processing location of thesample processing device. wherein the two or more different cartridgeseach has a different configuration for holding reagents.